8-4.1 Introduction

Gene therapy is one of the fastest developing fields of medicine as of today. About 500 clinical trials are being carried out globally in order to evaluate the efficiency of this treatment in different diseases. Gene therapy technique uses DNA to treat disease and it therapeutically alters the gene expression in a cell. Therapeutic proteins are produced by cloning the DNA into a vector and then by expressing that DNA inside the target cell of the patient which attempts to treat and address specific ailment. Gene therapy has gone through a series of triumphs and failures, which have generated both optimism and frustration at the same time.

8-4.2 Challenges in gene therapy

Although modification of germ-line cells at gene level offers the possibility of permanently eliminating certain genetic diseases, important ethical concerns, including eugenics (improvement of human race by selective breeding) and transfer of undesirable trait or side-effects to the patients' descendents, currently prohibit its development and therefore only somatic gene therapy is in progress. Gene therapy poses one of the greatest technical challenges in modern medicine especially since it is quite hard to introduce new genes into cells of the body partly due to a numbers of barriers. It faces numerous challenges as discussed below.

8-4.2.1. Gene delivery and activation

The prerequisite of gene therapy is the delivery of vectors to the target cells at the target area of tissue. The gene should be in higher concentration at the site of target cells so that the cells can easily take up the corrected or wild gene. When the gene reaches its destination it has to be activated to produce the desired protein encoded by that specific gene. However, such gene delivery and activation are the biggest obstacles faced by the gene therapy enthusiasts.

As far as choosing the best vector, there is no one "perfect vector" that can treat every disorder. Like any type of conventional medical therapy, gene therapy vector must be customized or tailor made to address the unique problem of the disease. Most commonly used gene therapy vectors are viral vectors which suffer from various disadvantages described in lecture 1 of module 8.

8-4.2.2. Introducing changes into the germ line

As told already targeting a gene to the correct cells is crucial for the success of any gene therapy. It is important to ensure that the gene of interest is not accidentally incorporated into the wrong cells which would cause the gene therapy to be inefficient and could develop a new health issues for the patient.

For instance, improper targeting could lead to incorporation of the therapeutic gene into patient's germ line, or reproductive cells that produce sperm and eggs. In such circumstances, the patient would pass on the delivered gene to their next generation. This could prevent the disease in future generation or it may result in unwanted consequences in foetus development. It has also ethical concerns as it involves genetic manipulation of an individual who is not yet born.

8-4.2. 3. Immune response

Gene delivery vectors must be able to escape the host's natural immune surveillance systems. Otherwise it can lead to serious illness or even death. One patient, who had a rare liver disorder, participated in a gene therapy trial at the University of Pennsylvania during 1999. But unfortunately, he died due to complications from inflammatory response after receiving a dose of experimental adenovirus mediated gene therapy for which US banned gene therapy trials for some time.